Platinum-Resistant Advanced Ovarian Cancer - Episode 7

Increase in PFS for Platinum-Resistant Advanced OC

March 15, 2019

Thomas C. Krivak, MD:Yeah, I think when you look at patients then recur, and we say,platinum resistant[or]platinum sensitive, some people are saying the better term at this point isplatinum not eligible. We’re trying to evolve that terminology ofplatinum resistant, but when you look at the trials that have been done in platinum resistant, the AURELIA trial was a great trial. It was very, in my mind, you know real-world, [in which] patients were either going to get treated with chemotherapy or chemotherapy and Avastin that recurred within 6 months. And and it was the treating physician [who] could choose between 3 choices of chemotherapy: weekly Taxol, Topotecan, or Doxil. So to me, I thought that was a [really], well, a real-world trial that, that we as clinicians could apply to our patients.

And what you saw was, you saw improvement in their response rate. You saw doubling of the progression-free survival [PFS], and you saw control of ascites. So to me, in patients who have platinum-resistant disease, I think that Avastin is 1 of the most important drugs for them, and combining that with chemotherapy does improve their progression-free survival [and] helps control their symptoms and increase their response rate. And again, it’s a safe drug because when you think of platinum-resistant disease, we had talked about signs of, you know, bowel obstruction and having defused disease within the abdomen, higher risk for bowel obstructions, bowel perforations, what you saw is that in the AURELIA trial, these patients tolerated their regimens very well and, again, doubling of the progression-free survival in a heart, in a difficult group of patients to treat is very, very important.

I would say in the platinum-resistant setting as well as the platinum-sensitive setting, we’re having studies now showing that bevacizumab after bevacizumab is safe and effective. So to me, I would use bevacizumab after bevacizumab. There [are] data in colorectal that the [MITO16MANGO2b] trial, which [were] presented at ASCO [the American Society of Clinical Oncology Annual Meeting] last year, showed that bevacizumab was safe and effective in the recurrent setting in using it up front as well as in the recurrent setting. So to me, I think it’s important that we always keep in the back of our minds that this is a very well-tolerated drug. It’s safe [and] easy to give, and patients can take their treatment [in the] up-front setting, in the recurrent setting, in both the platinum-sensitive as well as the platinum-resistant stage.

I think that Avastin is a great drug. Bevacizumab is a great drug. You know, when they developed it and it was a phase II, we saw excellent response rates. And when you look at the totality of the data for ICON7 and GOG-0218 [and] GOG-0213, which is platinum-sensitive recurrent; the OCEANS trial, which is platinum-sensitive recurrent; and the AURELIA trial, and the platinum-resistant recurrent, what you’re seeing is a drug that improves the response rates [and] improves the progression-free survival in specific studies, and GOG-0213 was a statistical significance improvement in overall survival. So the totality of the data [show] that this is a very safe drug.

I was fortunate enough to start using it back in 2005 [and] 2006, and I’ve always been a firm believer in maintenance therapy. To me I’ve always wanted to treat low-volume disease, try to improve each progression-free survival, progression-free survival 1, progression, because to me once we start improving all those progression-free survivals, that’s when you’re really going to start to make an improvement in overall survival. So I think overall survival at times is very challenging to look at, but to me it’s always, if we can improve PFS1, then let’s work on improving PFS2, and then we’re going to have really long, durable responses.

Transcript edited for clarity.


Case: A 70-Year-Old Woman Presenting With Advanced Ovarian Cancer

H & P:

  • A 70-year-old woman presents for evaluation of left-ovary mass discovered during a recent pelvic exam. She reports abdominal tenderness, urinary symptoms, and a “bloated” or “full” feeling, despite normal diet and bowel movements
  • Postmenopausal, no children
  • PE: reveals a woman of low normal weight (BMI = 19 kg/m2) with hypertension; abdomen is distended and shows dullness to percussion
    • BP = 135/80 mm Hg on metoprolol
    • Fasting glucose = 95 mg/dL
    • LDL = 90 mg/dL

Imaging

  • CT with contrast of pelvis, abdomen, and chest reveals multiple peritoneal lesions and spread to outside of liver
  • Malignant ascites present

Biopsy and labs:

  • Pathology: high-grade epithelioid adenosarcoma, ovarian primary
  • BRCA1/2status: unknown
  • CA-125: 656 U/mL

Treatment

  • She underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and tumor debulking; residual disease after cytoreduction: 1.25 cm
  • Diagnosis: stage IV ovarian cancer, grade 3
  • Started on carboplatin and paclitaxel plus bevacizumab; achieved a partial response
  • She was continued on maintenance bevacizumab

Follow up:

  • Follow up imaging at 6 months showed disease progression in the liver
  • She was started on paclitaxel plus bevacizumab